tbuckley/cabot-search huggingface dataset:
Patient-controlled subcutaneous analgesia with hydromorphone versus oral oxycodone for opioid titration of cancer pain: A prospective multicenter randomized trial.
Authors: Xiaoguang Xiao, Qian Chu, Yuan Chen
Journal: Journal of Clinical Oncology (2023)

12124 Background: Studies have shown that oral oxycodone sustained-release (SR) tablets can be used for opioid titration. The European Society for Medical Oncology (ESMO) guidelines for adult cancer pain recommend opioid titration through the parenteral route, usually the intravenous or subcutaneous route. Patient-controlled subcutaneous analgesia (PCSA) with hydromorphone needs further evaluation for opioid titration. This prospective multicenter study was designed to compare the efficacy and safety of hydromorphone PCSA with oral oxycodone SR tablets for opioid titration of cancer pain. Methods: Eligible patients with cancer pain were randomly assigned in a 1:1 ratio to the PCSA group or the oxycontin group for dose titration. Different titration methods were given in both groups depending on whether the patient had an opioid tolerance. The primary endpoint of this study was time to successful titration (TST). Results: A total of 256 patients completed this study. The PCSA group had a significantly lower TST compared with the oxycontin group (median [95% confidence interval (CI)], 5.5 [95%CI: 2.5-11.5] hours vs. 16.0 [95%CI: 11.5-22.5] hours; p&lt; 0.001). PCSA reduced the frequency of breakthrough pain (Btp), especially in patients with opioid tolerance. The number of Btp was 121±28 times and 186±31 times in the PCSA and oxycontin groups, respectively ( p&lt; 0.001). The 12-hour numeric rating scale (NRS) score was significantly lower in the PCSA group than that in the oxycontin group (median [95%CI], 2.5 [95%CI: 1.4-2.9] vs. 4.4[95%CI: 3.2-5.8]) ( p&lt; 0.001). Similar equivalent morphine consumption and significantly improved quality of life were observed in the two groups. No between-group difference in the incidence of opioid-related adverse effects was observed. Conclusions: Compared with oral oxycodone SR tablet, the use of PCSA with hydromorphone achieved faster pain relief and a shorter titration duration for patients with cancer pain without increasing adverse events. Clinical trial information: ChiCTR2000037845 .
Real-world impact of oncology education on clinical practices at five community cancer care centers.
Authors: Elizabeth Johnson, Margaret Stefan, Nicolette Theriault, Yael Waknine, Jared Weiss
Journal: Journal of Clinical Oncology (2023)

e23003 Background: Broad based molecular testing is an underutilized but essential factor in determining patient candidacy for frontline immunotherapy (IO) for advanced NSCLC. Findings from previous educational initiatives and real-world studies such as Nadler et al. and Velcheti, et al. indicate that understanding the importance of molecular testing to optimize therapy in NSCLC, remains an educational gap among oncology clinicians. Based on this real-world data, an educational initiative was developed to impart demonstrable change in clinician’s molecular testing practices and IO treatment selection. Methods: Grand round modules held at 5 community cancer centers facilitated learners’ ability to incorporate molecular testing and treatment strategies into clinical practice, which may improve patient outcomes. Physician leaders were leveraged at each center in order to increase learner engagement, encourage peer-to-peer learning and foster a learning community and potentially encourage institutional changes. Educational impact was assessed via a matched Pre/Post Test methodology which incorporated fact based and procedural information as well as asking learners to rate their confidence and intent to perform. To evaluate educational impact, pre and post educational intervention, 100 tumor board patient cases collected by OncoLens from the five centers were analyzed to assess any change in molecular testing practices, and therapeutic selection. Results: 174 learners participated in the grand round modules, results from matched Pre- and Post-Test showed significant improvements in overall proficiency, +51% in module 1 and +89% in module 2, alongside self-reported increased intent to utilize broad-based molecular testing +93% and IO +236% in advanced NSCLC. Post-intervention tumor board cases demonstrated that effective education can lead to real-world practice changes; there was an increase (+207%) in molecular testing of NSCLC, 75% increased use of liquid biopsy, the shift towards more comprehensive testing was accompanied by more judicious determination of IO candidacy, and a 52% increase in IO implementation. Additionally, feedback from the physician leaders reported that institutional changes were implemented following the educational initiative; 3 centers now actively consider liquid biopsy if tissue quantity is not sufficient (QNS), one institution has implemented reflex testing to improve time to treatment. Conclusions: Findings suggest that onsite CME/CE targeting understanding and proficiency in molecular testing for advanced NSCLC, can translate into real-world change to clinical practice that optimizes therapeutic decision-making in patient care; community cancer center case data supports the efficacy of the education on real-world clinical practices. Nadler E, et al.doi: 10.1016/j.ctarc.2022.100522. Velcheti V, et al.doi: 10.1371/journal.pone.0206370.
Sunvozertinib for the treatment of NSCLC with EGFR Exon20 insertion mutations: The first pivotal study results.
Authors: Mengzhao Wang, Yun Fan, Meili Sun, Yongsheng Wang, Yanqiu Zhao, Bo Jin, Ying Hu, Zhigang Han, Xia Song, Anwen Liu, Kejing Tang, Ding Cuimin, Li Liang, Lin Wu, Junzhen Gao, Jianghong Wang, Ying Cheng, Jianying Zhou, Yong He, Li Zheng
Journal: Journal of Clinical Oncology (2023)

9002 Background: Sunvozertinib(DZD9008) is a rationally designed selective, irreversible EGFR exon20 insertion (exon20ins) inhibitor with wild-type EGFR selectivity. Here we reported the results of WU-KONG6, the first pivotal study of sunvozertinib in previously treated NSCLC patients with EGFR exon20ins. Methods: WU-KONG6 (NCT05712902 and CTR20211009) is a phase II, multi-center pivotal study in NSCLC patients with EGFR exon20ins, whose diseases had progressed on or were after platinum-based chemotherapy. Tumor tissue EGFR exon20ins status was tested by local or central laboratory. The primary and key secondary endpoint were objective response rate (ORR) and duration of response (DoR), respectively, assessed by Blinded Independent Central Review (BICR). Patients received 300 mg sunvozertinib once daily until discontinuation criteria were met. Results: Between July 19, 2021, and May 6, 2022, a total of 104 Chinese patients were enrolled into WU-KONG6 study. The efficacy analysis set included 97 patients, whose EGFR exon20ins status was retrospectively confirmed by a central laboratory. A total of 30 different exon20ins subtypes were enrolled. The median age was 58 years; 59.8% (58/97) were female; 95.9% (93/97) were adenocarcinoma; 95.9% (93/97) had metastatic diseases at study entry; 32% (31/97) had baseline brain metastasis; the median prior lines of therapy were 2. By the data cutoff date (October 17, 2022), the BICR assessed confirmed ORR (cORR) was 60.8% (59/97). In patients with baseline brain metastasis, the cORR was 48.5% (15/31). Anti-tumor efficacy was observed irrespective of age, gender, smoking status, prior lines of therapies, prior onco-immunotherapies, mutation subtypes, and baseline brain metastasis. By the data cut-off date, median follow-up time for responders was 7.1 months, and 64.4% (38/59) of responders were still responding. The longest DoR was &gt; 11 months, and the median DoR has not been reached. The safety analysis set included all enrolled 104 patients. The most common treatment emergent adverse events (TEAEs) were similar as what have been previously reported for sunvozertinib, and also similar as that of other EGFR inhibitors. Majority of the TEAEs were grade 1 or 2, and clinically manageable. Conclusions: The first pivotal study results confirmed sunvozertinib’s superior anti-tumor efficacy than the current available therapy for NSCLC with EGFR exon20ins. The safety profile from WU-KONG6 study was consistent with previously reported findings. The updated data will be presented at the meeting. A multinational phase II pivotal study (WU-KONG1, NCT03974022) with the same study design is ongoing in the USA, Australia, and countries/regions in Asia, Europe and South America. Clinical trial information: NCT05712902 .
Management of tumor treating fields (TTFields) therapy-related skin adverse events in pleural mesothelioma: A single center experience of TTFields therapy concomitant with chemotherapy.
Authors: Federica Grosso, Sara Delfanti, Giulia Gallizzi, Francesca Marengo, Iacopo Megna, Carlotta Bertolina, Giovanni Luca Ceresoli
Journal: Journal of Clinical Oncology (2023)

e20542 Background: Tumor Treating Fields (TTFields) therapy is a noninvasive, locoregional modality comprised of electric fields which disrupt critical cellular processes necessary for cancer cell viability and tumor progression. TTFields therapy is FDA approved and CE-marked for glioblastoma, and pleural mesothelioma. Approval for the latter was based on results from the phase 2 STELLAR study (EF-23, NCT02397928), in which the median OS was 18.2 months (95% CI 12.1–25.8) and median PFS was 7.6 months (95% CI 6.7–8.6). As the electrical fields are delivered non-invasively via skin-adhered arrays, the most common adverse events (AEs) are mild-moderate skin reactions which can be effectively managed with appropriate prophylaxis and timely intervention. Here we report a single-center experience of treating and managing TTFields therapy-related AEs in the STELLAR study, based on a center-specific protocol. Methods: The STELLAR study was a multicenter, single-arm, non-randomized, phase 2 study, whereby patients received TTFields therapy (150 kHz, 18 h/day) concomitant with pemetrexed (500 mg/m 2 ) and platinum-based chemotherapy (75 mg/m 2 ). TTFields-therapy AEs were managed and treated using a center-specific protocol (Table). Results: In this single center, 23 patients were treated using the predefined protocol to prevent skin AEs; all were included in the safety analysis. n = 15 (65%) reported a mild-moderate skin AE (n = 12 [52%] medical device site reaction [skin AE], n = 1 [4%] had mild-moderate rash, rash erythematous and skin irritation) in the single center, vs n = 54 (68%) in the overall STELLAR population. n = 2 (9%) in the single site had a severe medical device site reaction, which was comparable with the overall STELLAR study population. Conclusions: A predefined multidisciplinary approach was successful to help prevent mild-moderate skin AEs. Timely and appropriate management of mild/moderate skin AEs can prevent exacerbations. Skin management may support usage, thus optimizing outcomes for patients. Guidelines on preventing skin AEs when using TTFields therapy are available and should be incorporated in a clinical setting. Clinical trial information: NCT02397928 . [Table: see text]
A retrospective single-centre analysis of the prevalence of statin use in geriatric oncology: Is there a role for cessation?
Authors: Darragh Thomas O'Sullivan, Anne Horgan, Rachel Clarke, Karine Ronan, Chris Cronin, Zelmarie Besalaar
Journal: Journal of Clinical Oncology (2023)

e24016 Background: Statins have become ubiquitous in medicine. There is a myriad of indications, and the duration of treatment required for efficacy is measured in years. There is a need for clarity on their role in geriatric oncology and when to de-prescribe. Within a sample of Irish patients in 1987, 8% would have been eligible for a statin. By 2016, this had climbed to 61%. During this time, the number needed to treat increased from 40 to 400. In terms of benefit, a meta-analysis concluded that 100 patients need treatment for 2.5 years to prevent one major adverse cardiovascular event (MACE) in the primary preventative setting. It is not clear whether this benefit is derived in later life. As a result, the United States preventive service task force concluded that evidence is insufficient to recommend initiating a statin for primary prevention in adults over 75. The aim of our study was to assess the prevalence of statin use in older adults with cancer, and the evidence for de-prescribing. Methods: Data was retrospectively collected from a prospectively maintained database of patients attending the Geriatric Oncology Assessment and Liaision (GOAL) clinic in the South East Cancer Centre, University Hospital Waterford, Ireland. Data collected includes age at cancer diagnosis, stage, co-morbidities, and medications. We determined how many patients were taking statins (or ezetimibe) prior to first oncology review, their indication and overall survival. Indications for statins were categorised using a hierarchy of indications, as described by Wallach Kildemoes et al. Results: 138 of 233 patients were taking statins at the time of their review (59%). The average age at cancer diagnosis was 78.6 years. Seventy-nine were taking statins for primary prevention (58%). 15 of 79 whom had diabetes. Stage 3 or 4 disease accounted for 78% of this group. Overall survival in this group was 1.59 years. Within the group with stage 4 disease (n = 100), 53 were taking a statin. Twenty-eight (52.8%) were for primary prevention. Within this group, 6 had diabetes. Overall survival in this group was 1.44 years. Conclusions: Overall survival of patients was short of the 2.5 years required to provide benefit. Therefore, there is evidence to stop this medication in the primary preventative group, once diagnosed with advanced cancer. The stage 4 disease group included patients undergoing secondary prevention, so treatment is more efficacious. However, with an overall survival of 1.44 years, the window for benefit is small.[Table: see text]
Subgroup analyses of primary refractory (refr) vs early relapsed (rel) large B-cell lymphoma (LBCL) from the TRANSFORM study of lisocabtagene maraleucel (liso-cel) vs standard of care (SOC) as second-line (2L) therapy.
Authors: Loretta J. Nastoupil, Manali K. Kamdar, Julio C. Chavez, Herve Ghesquieres, Monalisa Ghosh, Houston Holmes, Armando López Guillermo, Joaquin Martinez-Lopez, Urban Novak, Vincent Ribrag, Claire Roddie, Edmund K. Waller, Tatyana A Feldman, Allison Claire Rosenthal, Craig Sauter, Malte Von Bonin, Reem Karmali, Sandrine Montheard, Alessandro Previtali, Jeremy S. Abramson
Journal: Journal of Clinical Oncology (2023)

7526 Background: The TRANSFORM primary analysis (PA; NCT03575351) confirmed the superior efficacy of liso-cel vs SOC as 2L therapy in patients (pts) with primary refr or early rel LBCL (Abramson et al. Blood 2022). Response to first-line (1L) therapy (refr vs rel), which was a study randomization stratification factor, may influence future treatment response. Here, we present results for refr and rel LBCL subgroups from the TRANSFORM PA. Methods: TRANSFORM is a randomized phase 3 study of liso-cel vs SOC (salvage chemotherapy [CT] followed by high-dose CT [HDCT]/autologous SCT [ASCT]) in adults ≤ 75 y with LBCL primary refr to or rel ≤ 12 mo after 1L therapy and eligible for HDCT/ASCT. The primary endpoint was event-free survival (EFS); key secondary endpoints were CR rate, PFS, and OS. In this predefined subgroup analysis, refr was SD, PD, PR, or CR with rel &lt; 3 mo after 1L therapy; rel was CR with rel ≥ 3 mo and ≤ 12 mo after 1L therapy. Results: 92 pts were randomized to each arm. Most pts in the liso-cel and SOC arms had refr disease (73% and 76%, respectively; rel disease, 27% and 24%). Baseline characteristics in the refr and rel subgroups, respectively, were generally balanced: median LDH (U/L; liso-cel, 228.5 and 225; SOC, 259 and 259); median SPD (cm 2 ; liso-cel, 11 and 12; SOC, 15.5 and 18); high-grade B-cell lymphoma (liso-cel, 27% and 16%; SOC, 27% and 9%); diffuse LBCL not otherwise specified (liso-cel, 58% and 56%; SOC, 49% and 73%). Consistent with the overall study population, EFS, CR rate, and PFS favored liso-cel vs SOC in both subgroups (Table). Safety was also consistent. Grade ≥ 3 cytokine release syndrome (CRS) and neurological events (NE) were low in refr (1% and 4%) and rel (0 and 4%) subgroups, respectively, with no grade 4/5 CRS or NEs. Conclusions: In TRANSFORM, liso-cel showed benefits in EFS, PFS, and CR rate vs SOC irrespective of prior response to 1L therapy. As refr LBCL is historically difficult to treat, outcomes for liso-cel in this subgroup are encouraging. Clinical trial information: NCT03575351 . [Table: see text]
The effect of LNS8801 alone and in combination with pembrolizumab in patients with metastatic uveal melanoma.
Authors: Alexander Noor Shoushtari, Marya F. Chaney, Justine Vanessa Cohen, Tina Garyantes, Jessica Jiyeong Lin, Jeffrey Joseph Ishizuka, Alain C. Mita, Monica M. Mita, Carolyn Muller, Christopher Natale, Marlana M. Orloff, Kyriakos P. Papadopoulos, Sapna Pradyuman Patel, Jordi Rodon Ahnert
Journal: Journal of Clinical Oncology (2023)

9543 Background: LNS8801 is an oral, selective, small molecule agonist of the G-protein coupled estrogen receptor (GPER). LNS8801 treatment results in increased melanocytic differentiation, reduced c-Myc protein levels in cancer cells, inhibition of proliferation, suppression of invasion, and enhancement of immune recognition. In preclinical models, LNS8801 has demonstrated increased activity in combination with immune checkpoint inhibitors (ICIs). In the first-in-human dose escalation study, LNS8801 was safe and tolerable alone and in combination with pembrolizumab in patients with advanced solid tumors (NCT04130516). Methods: Patients with measurable metastatic uveal melanoma (mUM) received LNS8801 (125 mg, QD, PO) alone or with pembrolizumab (200 mg, Q3W, IV) (NCT04130516). The primary objective was safety and tolerability assessed according to NCI CTCAE v5.0. Secondary endpoints include pharmacokinetic, pharmacodynamics, objective response rate (ORR) and disease control rate (DCR, CR+PR+SD) per RECIST v1.1. Presence of a consensus, fully-functional, germline GPER coding sequence was assessed via Sanger sequencing on DNA extracted from blood as a potential predictive biomarker. Results: As of 1/25/23, 15 patients with mUM were treated with LNS8801 alone (n = 8) or a combination of LNS8801 and pembrolizumab (n = 7). Patients were previously treated with a median of 2 prior lines of systemic therapy. 4 of 8 monotherapy patients had AEs potentially related to study drug (all grade 1), with no AEs occurring in more than one patient. 6 of 7 combination patients had AEs potentially related to study drugs (grades 1-2), with fatigue occurring in more than one patient. Of the 14 patients evaluable for efficacy (7 mono, 7 combo), 7 had disease control (4 mono, 3 combo) resulting in a disease control rate of 50%. 1 patient treated with combination achieved a confirmed partial response. Consensus germline GPER was present in 2 of 12 sequenced patients (1 mono, 1 combo), and both of these patients have ongoing disease control lasting longer than 24 weeks. Conclusions: LNS8801 alone and in combination with pembrolizumab is tolerable without unanticipated toxicities and demonstrates encouraging anti-tumor activity in patients with mUM. The hypofunctional germline GPER variant appears over-represented in this cohort compared to the normal population, suggesting a potential significant role for GPER in the development of mUM. These data support further development of LNS8801 alone and in combination with pembrolizumab as a therapeutic approach to treat mUM patients, especially for patients with consensus germline GPER. Clinical trial information: NCT04130516 .
Assessing the efficacy and safety of DEB-BACE combined with intravenous chemotherapy for the treatment of intermediate to advanced lung adenocarcinoma after progression of targeted drug resistance.
Authors: Lingqiang Lai, Jianfei Tu, Dengke Zhang, Xihui Ying, Jiahao Wu, Jie Chen, Li Chen
Journal: Journal of Clinical Oncology (2023)

8555 Background: To compare the efficacy and safety of drug-eluting bead bronchial arterial chemoembolization (DEB-BACE) combined with intravenous chemotherapy versus systemic intravenous chemotherapy for intermediate to advanced lung adenocarcinoma with positive driver genes after progression of targeted therapy. Methods: A total of 131 patients with intermediate to advanced lung adenocarcinoma were retrospectively recruited from 2018-2022 and divided into Group A (standard chemotherapy regimen, N=62) and Group B (DEB-BACE and intravenous chemotherapy, N=69). The short-term efficacy, hemoptysis remission rate, dyspnea remission rate, and incidence of adverse effects were compared between the two groups using the χ2 test. Survival estimates were performed by Kaplan-Meier, and a Log-rank test was performed to examine survival differences between groups. Results: The three-month disease control rate (DCR: 82.6% vs 58.1%) and objective remission rate (ORR: 60.9% vs 38.7%) were better in group B than in group A (both P&lt;0.05). Median progression-free survival (PFS, 10.0 vs 7.9 months) and median overall survival (OS, 33.0 vs 18.0 months) were better in group B than in group A (both P &lt; 0.05). The PFS rates at 6, 12, and 24 months were 67.3%, 40.8%, and 0.0% and 54.1%, 23.2%, and 0.0% in groups B and A, respectively; and the OS rates at 6, 12, and 24 months were 100%, 95.7%, 72%, 88.6%, 66.1%, and 21.8% in group B and group A, respectively, with statistically significant differences (P &lt; 0.05). Within one month after treatment, group B had better hemoptysis relief (83.3% vs. 20.0%) and dyspnea relief (57.5% vs. 30.0%) than group A (both P &lt; 0.05). During the follow-up period, the incidence of adverse reactions was significantly lower in group B than in group A (P &lt; 0.05). Conclusions: For patients with intermediate to advanced lung adenocarcinoma who have failed to progress on targeted therapy, DEB-BACE combined with intravenous chemotherapy has shown superior efficacy and survival benefit and lower adverse effects, while significantly improving patients' symptoms of hemoptysis and dyspnea, with important application prospects.